T cells are involved in the immune response and are primarily involved in cellular immunity, such as guarding against virally infected cells, fungi, parasites and foreign tissue.
Briefly, T cells are activated by binding to antigen-displaying macrophages. However, the T cell receptor must specifically complex with the antigen and a Major Histocompatibility Complex (MHC) protein displayed on the surface of the macrophage.
The binding induces the macrophage to release interleukin-1, a polypeptide growth factor, which stimulates the bound T cell to proliferate and differentiate. This proliferation and differentiation is enhanced by the T cells autostimulatory secretion interleukin-2. The T cell can differentiate into a number of different phenotypes, such as cytotoxic T cells which are specifically targeted to antigen displaying host cells and are capable of lysing the cell, helper T cells which are involved in activating cytotoxic T cells and in co-operating with B cells to produce antibodies and memory T cells which upon re-encountering their cognate antigen proliferate at a faster rate than non-memory T cells.
It will be apparent to one skilled in the art that the activation of T cells is an important step in the immunological response. By manipulating the activation of T cells it will be possible to obtain useful immunological products and develop more efficient treatment techniques.
Previously, to achieve T cell activation, a macrophage displaying an antigen and an MHC protein was required. A number of problems and drawbacks are associated with this, a major drawback being that only T cells specific for the antigen are activated. Other T cells not specific for the antigen remain unactivated. Other problems may arise if the desired antigen is difficult to obtain or hazardous to work with. Additionally, if an antigen is used in cell culture to achieve activation and it is not easy to remove, contamination problems may occur.
The same problems will occur in vivo and it is obviously undesirable to infect an individual with an antigenic substance.
By achieving antigen independent T cell activation it will be possible to activate a population of T cells without the need to isolate and display an antigen on the surface of a macrophage.
It is known that interleukin-2 is potent T-lymphocyte growth enhancer and the use of interleukin-2 as an adjuvant has been described. In this role interleukin-2 was thought to function as an expander of the population of already activated T-lymphocytes. However, it was not known that interleukin-2 (in combination with other cytokines) could act specifically to activate T-lymphocytes in an antigen independent manner.